Microbiology or Immunology
Canonical PI3Kγ signaling in myeloid cells restricts Trypanosoma cruzi infection and dampens chagasic myocarditis.
Chagas disease is caused by infection with the protozoan Trypanosoma cruzi (T. cruzi) and is an important cause of severe inflammatory heart disease. However, the mechanisms driving Chagas disease cardiomyopathy have not been completely elucidated. Here, we show that the canonical PI3Kγ pathway is upregulated in both human chagasic hearts and hearts of acutely infected mice. PI3Kγ-deficient mice and mutant mice carrying catalytically inactive PI3Kγ are more susceptible to T. cruzi infection. The canonical PI3Kγ signaling in myeloid cells is essential to restrict T. cruzi heart parasitism and ultimately to avoid myocarditis, heart damage, and death of mice. Furthermore, high PIK3CG expression correlates with low parasitism in human Chagas' hearts. In conclusion, these results indicate an essential role of the canonical PI3Kγ signaling pathway in the control of T. cruzi infection, providing further insight into the molecular mechanisms involved in the pathophysiology of chagasic heart disease.
Authors
Maria C Silva; Marcela Davoli-Ferreira; Tiago S Medina; Renata Sesti-Costa; Grace K Silva; Carla D Lopes; Lucas E Cardozo; Fábio N Gava; Konstantina Lyroni; Fabrício C Dias; Amanda F Frade; Monique Baron; Helder I Nakaya; Florêncio Figueiredo; José C Alves-Filho; Fernando Q Cunha; Christos Tsatsanis; Christophe Chevillard; Edecio Cunha-Neto; Emilio Hirsch; João S Silva; Thiago M Cunha
External link
Publication Year
2018
Publication Journal
Nature communications
Associeted Project
Microbiology or Immunology
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